New C-protective group for peptide synthesis. Application of 2-(1-adamantyl)-propanol-2 esters.

Abstract

To investigate the possibility of using the 2-(1-adamantyl)-2-propyl (Adp) ester group for carboxyl protection during peptide synthesis, the tetrapeptide Boc-Phe-Arg(NO2)-Phe-Pro-OAdp (IV) was prepared by the carbodiimide method. In this synthesis the Z group was removed by transfer hydrogenation and the Nps group by treatment with 2-thiopyridone. The Adp group was then cleaved with 3% TFA/DCM, yielding Boc-Phe-Arg(NO2)-Phe-Pro-OH. For subsequent kinetics studies the decapeptide Boc-Leu--Z-Orn-Arg(NO2)-Pro- Pro-Gly-Phe-Ser(Bzl)-Pro-Pro-OAdp (VIII) was synthesized by a 9 + 1 scheme. This peptide was also selectively deblocked. Comparing reaction abilities of Z-Pro-OAdp and Z-Pro-OBut, it was demonstrated that the Adp ester is cleaved by 3% TFA/DCM 230 times faster than the Bu(t) ester. For peptides IV and VIII the ratios between the rates of competitive elimination of the Adp and Boc groups by 3% TFA/DCM are 19 and 64, respectively.